Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M010238200 on February 15, 2001

J. Biol. Chem., Vol. 276, Issue 20, 17354-17360, May 18, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/20/17354    most recent
M010238200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Li, Z.
Right arrow Articles by Sacks, D. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, Z.
Right arrow Articles by Sacks, D. B.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Calmodulin Enhances the Stability of the Estrogen Receptor*

Zhigang Li, John L. JoyalDagger , and David B. Sacks§

From the Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115

The estrogen receptor mediates breast cell proliferation and is the principal target for chemotherapy of breast carcinoma. Previous studies have demonstrated that the estrogen receptor binds to calmodulin-Sepharose in vitro. However, the association of endogenous calmodulin with endogenous estrogen receptors in intact cells has not been reported, and the function of the interaction is obscure. Here we demonstrate by co-immunoprecipitation from MCF-7 human breast epithelial cells that endogenous estrogen receptors bind to endogenous calmodulin. Estradiol treatment of the cells had no significant effect on the interaction. However, incubation of the cells with tamoxifen enhanced by 5-10-fold the association of calmodulin with the estrogen receptor and increased the total cellular content of estrogen receptors by 1.5-2-fold. In contrast, the structurally distinct calmodulin antagonists trifluoperazine and CGS9343B attenuated the interaction between calmodulin and the estrogen receptor and dramatically reduced the number of estrogen receptors in the cell. Neither of these agents altered the amount of estrogen receptor mRNA, suggesting that calmodulin stabilizes the protein. This hypothesis is supported by the observation that, in the presence of Ca2+, calmodulin protected estrogen receptors from in vitro proteolysis by trypsin. Furthermore, overexpression of wild type calmodulin, but not a mutant calmodulin incapable of binding Ca2+, increased the concentration of estrogen receptors in MCF-7 cells, whereas transient expression of a calmodulin inhibitor peptide reduced the estrogen receptor concentration. These data demonstrate that calmodulin binds to the estrogen receptor in intact cells in a Ca2+-dependent, but estradiol-independent, manner, thereby modulating the stability and the steady state level of estrogen receptors.

* This work was supported in part by a grant from the National Institutes of Health (to D. B. S.) and a Breast Cancer Research Grant from the Massachusetts Department of Public Health (to J. L. J.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Current address: Praecis Pharmaceuticals, Inc., One Hampshire St., Cambridge, MA 02139.

§ To whom correspondence should be addressed: Brigham and Women's Hospital, Thorn 530, 75 Francis St., Boston, MA 02115. Tel.: 617-732-6627; Fax: 617-278-6921; E-mail: dsacks@rics.bwh.harvard.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Hum ReprodHome page
E. Kondoh, T. Okamoto, T. Higuchi, K. Tatsumi, T. Baba, S. K. Murphy, K. Takakura, I. Konishi, and S. Fujii
Stress affects uterine receptivity through an ovarian-independent pathway
Hum. Reprod., April 1, 2009; 24(4): 945 - 953.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
N. Vasudevan and D. W. Pfaff
Membrane-Initiated Actions of Estrogens in Neuroendocrinology: Emerging Principles
Endocr. Rev., February 1, 2007; 28(1): 1 - 19.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
A. Uttenweiler, H. Schwarz, H. Neumann, and A. Mayer
The Vacuolar Transporter Chaperone (VTC) Complex Is Required for Microautophagy
Mol. Biol. Cell, January 1, 2007; 18(1): 166 - 175.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Li, Z. Li, P. M. Howley, and D. B. Sacks
E6AP and Calmodulin Reciprocally Regulate Estrogen Receptor Stability
J. Biol. Chem., January 27, 2006; 281(4): 1978 - 1985.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Katou, E. Karita, H. Yamakawa, S. Seo, I. Mitsuhara, K. Kuchitsu, and Y. Ohashi
Catalytic Activation of the Plant MAPK Phosphatase NtMKP1 by Its Physiological Substrate Salicylic Acid-induced Protein Kinase but Not by Calmodulins
J. Biol. Chem., November 25, 2005; 280(47): 39569 - 39581.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Li, Z. Li, and D. B. Sacks
The Transcriptional Activity of Estrogen Receptor-{alpha} Is Dependent on Ca2+/Calmodulin
J. Biol. Chem., April 1, 2005; 280(13): 13097 - 13104.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. del Rio, J. M. G. Pedrero, C. Martinez-Campa, P. Zuazua, P. S. Lazo, and S. Ramos
Melatonin, an Endogenous-specific Inhibitor of Estrogen Receptor {alpha} via Calmodulin
J. Biol. Chem., September 10, 2004; 279(37): 38294 - 38302.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
E. Cifuentes, J. M. Mataraza, B. A. Yoshida, M. Menon, D. B. Sacks, E. R. Barrack, and G. P.-V. Reddy
Physical and functional interaction of androgen receptor with calmodulin in prostate cancer cells
PNAS, January 13, 2004; 101(2): 464 - 469.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
E. T. Alarid, M. T. Preisler-Mashek, and N. M. Solodin
Thyroid Hormone Is an Inhibitor of Estrogen-Induced Degradation of Estrogen Receptor-{alpha} Protein: Estrogen-Dependent Proteolysis Is Not Essential for Receptor Transactivation Function in the Pituitary
Endocrinology, August 1, 2003; 144(8): 3469 - 3476.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Li, Z. Li, and D. B. Sacks
Calmodulin Regulates the Transcriptional Activity of Estrogen Receptors. SELECTIVE INHIBITION OF CALMODULIN FUNCTION IN SUBCELLULAR COMPARTMENTS
J. Biol. Chem., January 3, 2003; 278(2): 1195 - 1200.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement